The combination of diclofenac and B vitamins – effectiveness and safety in clinical practice Review article
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Published:
Mar 31, 2021
Keywords:
COX-1, COX-2, cardiovascular risk, NSAID, low back pain
Main Article Content
Abstract
Diclofenac is one of the most commonly used non-steroidal anti-inflammatory drugs in the World, eagerly chosen for the therapy of skeletal, joint and muscle pain. However, the use of diclofenac is associated with side effects common for the entire class of drugs, including enhancement of cardiovascular risk. It has been shown that B vitamins are involved in many processes essential for the nervous system activity, as well as in the mechanism of initiating and transmitting pain stimuli. Besides, they have a synergistic analgesic effect when combined with diclofenac. Application of both drugs in analgesic therapy resulted in more effective pain relief, but also allowed for the reduction of diclofenac doses, leading to minimize the risk of side effects. The combination of B vitamins has a positive effect on the efficacy and safety of the therapy, which is important especially for low cardiovascular risk patients.
Article Details
How to Cite
Postuła, M., Czajka , P., & Fitas , A. (2021). The combination of diclofenac and B vitamins – effectiveness and safety in clinical practice. Medycyna Faktow (J EBM), 14(1(50), 44-51. https://doi.org/10.24292/01.MF.0121.5
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References
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6. León-Reyes MR, Castañeda-Hernández G, Ortiz MI. Pharmacokinetic of diclofenac in the presence and absence of glibenclamide in the rat. J Pharm Pharm Sci. 2009; 12(3): 280-7.
7. Ortiz MI. Blockade of the antinociception induced by diclofenac, but not of indomethacin, by sulfonylureas and biguanides. Pharmacol Biochem Behav. 2011; 99: 1-6.
8. Benson MD, Aldo-Benson M, Brandt KD. Synovial fluid concentrations of diclofenac in patients with rheumatoid arthritis or osteoarthritis. Semin Arthritis Rheum. 1985; 15: 65-7.
9. Van Hecken A, Schwartz JI, Depré M et al. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000; 40: 1109-20.
10. Bhala N, Emberson J, Merhi A et al.; on behalf of the Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013; 382(9894): 769-79.
11. Patrono C, Baigent C. Nonsteroidal Anti-Inflammatory Drugs and the Heart. Circulation. 2014; 129(8): 907-16. http://doi.org/10.1161/CIRCULATIONAHA.113.004480.
12. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy – A Review. Nutrients. 2016; 8: 68.
13. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011; 437: 357-72.
14. Zimmermann M. Possibilities for B-vitamins to modulate basic biological mechanisms involved in pain. In: Gerbershagen HU, Zimmermann M (ed). B-Vitamins in Pain. pmi-Verlag, Frankfurt 1988: 1-8.
15. Altun I, Kurutaş EB. Vitamin B complex and vitamin B12 levels after peripheral nerve injury. Neural Regen Res. 2016; 11(5): 842-5.
16. Izhar M, Alausa T, Folker A et al. Effects of COX inhibition on blood pressure and kidney function in ACE inhibitor-treated blacks and hispanics. Hypertension. 2004; 43: 573-7.
17. Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018; 362: k3426.
18. Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest. 2006; 116(1): 4-15.
19. Zingler G, Hermann B, Fischer T et al. Cardiovascular adverse events by non-steroidal anti-inflammatory drugs: when the benefits outweigh the risks. Expert Rev Clin Pharmacol. 2016; 9: 1479-92.
20. Haupt E, Ledermann H, Köpcke W. Benfotiamine in the treatment of diabetic polyneuropathy – a three-week randomized, controlled pilot study (BEDIP Study). Int J Clin Pharmacol Ther. 2005; 43(2): 71-7. http://doi.org/10.5414/cpp43071.
21. Meador KJ, Nichols ME, Franke P. Evidence for a central cholinergic effect of high‐dose thiamine. Ann Neurol. 1993; 34(5): 724-6.
22. Fu QG, Carstens E, Stelzer B et al. B vitamins suppress spinal dorsal horn nociceptive neurons in the cat. Neurosci Lett. 1988; 95: 192-7.
23. Jolivalt CG, Mizisin LM, Nelson A et al. B vitamins alleviate indices of neuropathic pain in diabetic rats. Eur J Pharmacol. 2009; 612: 41-7.
24. Song X-S, Huang Z-J, Song X-J. Thiamine suppresses thermal hyperalgesia, inhibits hyperexcitability, and lessens alterations of sodium currents in injured, dorsal root ganglion neurons in rats. Anesthesiology. 2009; 110(2): 387-400.
25. Reyes-García G, Medina-Santillán R, Flores-Murrieta FJ et al. Analgesic effects of B vitamins: a review. Curr Topics Pharmacol. 2006; 10(1): 1-31.
26. Rocha-González HI, Terán-Rosales F, Reyes-García G et al. B vitamins increase the analgesic effect of diclofenac in the rat. Proc West Pharmacol Soc. 2004; 47: 84-7.
27. Hoy D, Bain C, Williams G et al. A systematic review of the global prevalence of low back pain. Arthritis Rheum. 2012; 64: 2028-37.
28. Bartoszyk GD, Wild A. B-vitamins potentiate the antinociceptive effect of diclofenac in carrageenin-induced hyperalgesia in the rat tail pressure test. Neurosci Lett. 1989; 101: 95-100.
29. Brüggemann G, Koehler CO, Koch EM. Results of a double-blind study of diclofenac + vitamin B1, B6, B12 versus diclofenac in patients with acute pain of the lumbar vertebrae. A multicenter study. Klin Wochenschr. 1990; 68(2): 116-20.
30. Levin OS, Moseĭkin IA. Vitamin B complex (milgamma) in the treatment of vertebrogenic lumbosacral radiculopathy. Zh Nevrol Psikhiatr Im S S Korsakova. 2009; 109(10): 30-5.
31. Mibielli MA, Geller M, Cohen JC et al. Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study. Curr Med Res Opin. 2009; 25(11): 2589-99. http://doi.org/10.3111/13696990903246911.
32. Enthoven WTM, Roelofs PD, Deyo RA et al. Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database Syst Rev. 2016; 2(2): CD012087. http://doi.org/10.1002/14651858.cd012087.
33. Márquez M, Guzman S. Systemic Review on the Use of Diclofenac/B Complex as an Anti-Inflammatory Treatment with Pain Relief Effect for Patients with Acute Lower Back Pain. Journal of Pain & Relief. 2015; 04(06): 1000216. http://doi.org/10.4172/2167-0846.1000216.
34. Geller M, Mibielli MA, Nunes CP et al. Comparison of the action of diclofenac alone versus diclofenac plus B vitamins on mobility in patients with low back pain. J Drug Assess. 2016; 5(1): 1-3. http://doi.org/10.3109/21556660.2016.1163263.
35. Cooper C, Chapurlat R, Al-Daghri N et al. Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Drugs Aging. 2019; 36: 15-24.
36. Elliott WJ. Do the blood pressure effects of nonsteroidal antiinflammatory drugs influence cardiovascular morbidity and mortality? Curr Hypertens Rep. 2010; 12: 258-66.
37. Chan CC, Reid CM, Aw T-J et al. Do COX-2 inhibitors raise blood pressure more than nonselective NSAIDs and placebo? An updated meta-analysis. J Hypertens. 2009; 27(12): 2332-41. http://doi.org/10.1097/hjh.0b013e3283310dc9.
38. Brater DC. Resistance to Loop Diuretics Why it Happens and What to Do About It. Drugs. 1985; 30(5): 427-43. http://doi.org/10.2165/00003495-198530050-00003.
39. Laiwah AC, Mactier RA. Antagonistic effect of non-steroidal anti-inflammatory drugs on frusemide-induced diuresis in cardiac failure. Br Med J. 1981; 283(6293): 714.
40. Bhagat K. Effects of non-steroidal anti-inflammatory drugs on hypertension control using angiotensin converting enzyme inhibitors and thiazide diuretics. East Afr Med J. 2001; 78: 507-9.
41. Palmer R, Weiss R, Zusman RM et al. Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors. Am J Hypertens. 2003; 16: 135-9.
42. White WB. Defining the problem of treating the patient with hypertension and arthritis pain. Am J Med. 2009; 122: S3-9.
43. Webster J. Interactions of NSAIDs with diuretics and beta-blockers mechanisms and clinical implications. Drugs. 1985; 30: 32-41.
44. Krum H, Swergold G, Curtis SP et al. Factors associated with blood pressure changes in patients receiving diclofenac or etoricoxib: results from the MEDAL study. J Hypertens. 2009; 27: 886-93.
45. Pavlicević I, Kuzmanić M, Rumboldt M et al. Interaction between antihypertensives and NSAIDs in primary care: a controlled trial. Can J Clin Pharmacol. 2008; 15: e372-82.
46. Sharman JE, La Gerche A, Coombes JS. Exercise and cardiovascular risk in patients with hypertension. Am J Hypertens. 2015; 28: 147-58.
47. Dong Y-H, Chang C-H, Wu L-C et al. Comparative cardiovascular safety of nonsteroidal anti-inflammatory drugs in patients with hypertension: a population-based cohort study. Br J Clin Pharmacol. 2018; 84: 1045-56.
48. Bruno A, Tacconelli S, Patrignani P. Variability in the response to non-steroidal anti-inflammatory drugs: mechanisms and perspectives. Basic Clin Pharmacol Toxicol. 2014; 114: 56-63.
49. Odom DM, Mladsi DM, Saag KG et al. Relationship between diclofenac dose and risk of gastrointestinal and cardiovascular events: meta-regression based on two systematic literature reviews. Clin Ther. 2014; 36: 906-17.
50. Moore N, Salvo F, Duong M et al. Cardiovascular risks associated with low-dose ibuprofen and diclofenac as used OTC. Expert Opin Drug Saf. 2014; 13: 167-79.
51. García Rodríguez LA, Tacconelli S, Patrignani P. Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol. 2008; 52(20): 1628-36.
52. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011; 8: e1001098.
53.Varas-Lorenzo C, Castellsague J, Stang MR et al. The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada. Pharmacoepidemiol Drug Saf. 2009; 18(11): 1016-25. http://doi.org/10.1002/pds.1815.
54. Andersohn F, Suissa S, Garbe E. Use of First- and Second-Generation Cyclooxygenase-2–Selective Nonsteroidal Antiinflammatory Drugs and Risk of Acute Myocardial Infarction. Circulation. 2006; 113(16): 1950-7. http://doi.org/10.1161/CIRCULATIONAHA.105.602425.
55. Salvo F, Antoniazzi S, Duong M et al. Cardiovascular events associated with the long-term use of NSAIDs: a review of randomized controlled trials and observational studies. Expert Opin Drug Saf. 2014; 13: 573-85.
56. Abdulmajeed NA, Alnahdi HS, Ayas NO et al. Amelioration of cardiotoxic impacts of diclofenac sodium by vitamin B complex. Eur Rev Med Pharmacol Sci. 2015; 19: 671-81.
57. Tanaka T, Kono T, Terasaki F et al. Thiamine prevents obesity and obesity-associated metabolic disorders in OLETF rats. J Nutr Sci Vitaminol. 2010; 56: 335-46.
58. Babaei-Jadidi R, Karachalias N, Kupich C et al. High-dose thiamine therapy counters dyslipidaemia in streptozotocin-induced diabetic rats. Diabetologia. 2004; 47(12): 2235-46.
59. Earnest CP, Wood KA, Church TS. Complex multivitamin supplementation improves homocysteine and resistance to LDL-C oxidation. J Am Coll Nutr. 2003; 22: 400-7.
60. Göksemin A, Sati L, Seval Y et al. Effects of Excess Vitamin B6 Intake on Serum Lipid Profile and Cerebral Cortex in Rats. Turk J Med Sci. 2006; 36(6): 327-35.
61. Schuijt MP, Huntjens-Fleuren HWHA, de Metz M et al. The interaction of ibuprofen and diclofenac with aspirin in healthy volunteers. Br J Pharmacol. 2009; 157: 931-4.
62. Catella-Lawson F, Reilly MP, Kapoor SC et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001; 345: 1809-17.
63. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. 2019.
64. Diclofenac-containing medicines 2013.
65. Altman R, Bosch B, Brune K et al. Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology. Drugs. 2015; 75: 859-77.
2. Meek IL, Van de Laar MAFJ, E Vonkeman H. Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks. Pharmaceuticals. 2010; 3(7): 2146-62.
3. Edwards SR, Mather LE, Lin Y et al. Glutamate and kynurenate in the rat central nervous system following treatments with tail ischaemia or diclofenac. J Pharm Pharmacol. 2000; 52(1): 59-66.
4. Voilley N, de Weille J, Mamet J et al. Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci. 2001; 21(20): 8026-33.
5. Ortiz MI, Granados-Soto V, Castañeda-Hernández G. The NO–cGMP–K+ channel pathway participates in the antinociceptive effect of diclofenac, but not of indomethacin. Pharmacol Biochem Behav. 2003; 76(1): 187-95.
6. León-Reyes MR, Castañeda-Hernández G, Ortiz MI. Pharmacokinetic of diclofenac in the presence and absence of glibenclamide in the rat. J Pharm Pharm Sci. 2009; 12(3): 280-7.
7. Ortiz MI. Blockade of the antinociception induced by diclofenac, but not of indomethacin, by sulfonylureas and biguanides. Pharmacol Biochem Behav. 2011; 99: 1-6.
8. Benson MD, Aldo-Benson M, Brandt KD. Synovial fluid concentrations of diclofenac in patients with rheumatoid arthritis or osteoarthritis. Semin Arthritis Rheum. 1985; 15: 65-7.
9. Van Hecken A, Schwartz JI, Depré M et al. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000; 40: 1109-20.
10. Bhala N, Emberson J, Merhi A et al.; on behalf of the Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013; 382(9894): 769-79.
11. Patrono C, Baigent C. Nonsteroidal Anti-Inflammatory Drugs and the Heart. Circulation. 2014; 129(8): 907-16. http://doi.org/10.1161/CIRCULATIONAHA.113.004480.
12. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy – A Review. Nutrients. 2016; 8: 68.
13. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011; 437: 357-72.
14. Zimmermann M. Possibilities for B-vitamins to modulate basic biological mechanisms involved in pain. In: Gerbershagen HU, Zimmermann M (ed). B-Vitamins in Pain. pmi-Verlag, Frankfurt 1988: 1-8.
15. Altun I, Kurutaş EB. Vitamin B complex and vitamin B12 levels after peripheral nerve injury. Neural Regen Res. 2016; 11(5): 842-5.
16. Izhar M, Alausa T, Folker A et al. Effects of COX inhibition on blood pressure and kidney function in ACE inhibitor-treated blacks and hispanics. Hypertension. 2004; 43: 573-7.
17. Schmidt M, Sørensen HT, Pedersen L. Diclofenac use and cardiovascular risks: series of nationwide cohort studies. BMJ. 2018; 362: k3426.
18. Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest. 2006; 116(1): 4-15.
19. Zingler G, Hermann B, Fischer T et al. Cardiovascular adverse events by non-steroidal anti-inflammatory drugs: when the benefits outweigh the risks. Expert Rev Clin Pharmacol. 2016; 9: 1479-92.
20. Haupt E, Ledermann H, Köpcke W. Benfotiamine in the treatment of diabetic polyneuropathy – a three-week randomized, controlled pilot study (BEDIP Study). Int J Clin Pharmacol Ther. 2005; 43(2): 71-7. http://doi.org/10.5414/cpp43071.
21. Meador KJ, Nichols ME, Franke P. Evidence for a central cholinergic effect of high‐dose thiamine. Ann Neurol. 1993; 34(5): 724-6.
22. Fu QG, Carstens E, Stelzer B et al. B vitamins suppress spinal dorsal horn nociceptive neurons in the cat. Neurosci Lett. 1988; 95: 192-7.
23. Jolivalt CG, Mizisin LM, Nelson A et al. B vitamins alleviate indices of neuropathic pain in diabetic rats. Eur J Pharmacol. 2009; 612: 41-7.
24. Song X-S, Huang Z-J, Song X-J. Thiamine suppresses thermal hyperalgesia, inhibits hyperexcitability, and lessens alterations of sodium currents in injured, dorsal root ganglion neurons in rats. Anesthesiology. 2009; 110(2): 387-400.
25. Reyes-García G, Medina-Santillán R, Flores-Murrieta FJ et al. Analgesic effects of B vitamins: a review. Curr Topics Pharmacol. 2006; 10(1): 1-31.
26. Rocha-González HI, Terán-Rosales F, Reyes-García G et al. B vitamins increase the analgesic effect of diclofenac in the rat. Proc West Pharmacol Soc. 2004; 47: 84-7.
27. Hoy D, Bain C, Williams G et al. A systematic review of the global prevalence of low back pain. Arthritis Rheum. 2012; 64: 2028-37.
28. Bartoszyk GD, Wild A. B-vitamins potentiate the antinociceptive effect of diclofenac in carrageenin-induced hyperalgesia in the rat tail pressure test. Neurosci Lett. 1989; 101: 95-100.
29. Brüggemann G, Koehler CO, Koch EM. Results of a double-blind study of diclofenac + vitamin B1, B6, B12 versus diclofenac in patients with acute pain of the lumbar vertebrae. A multicenter study. Klin Wochenschr. 1990; 68(2): 116-20.
30. Levin OS, Moseĭkin IA. Vitamin B complex (milgamma) in the treatment of vertebrogenic lumbosacral radiculopathy. Zh Nevrol Psikhiatr Im S S Korsakova. 2009; 109(10): 30-5.
31. Mibielli MA, Geller M, Cohen JC et al. Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study. Curr Med Res Opin. 2009; 25(11): 2589-99. http://doi.org/10.3111/13696990903246911.
32. Enthoven WTM, Roelofs PD, Deyo RA et al. Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database Syst Rev. 2016; 2(2): CD012087. http://doi.org/10.1002/14651858.cd012087.
33. Márquez M, Guzman S. Systemic Review on the Use of Diclofenac/B Complex as an Anti-Inflammatory Treatment with Pain Relief Effect for Patients with Acute Lower Back Pain. Journal of Pain & Relief. 2015; 04(06): 1000216. http://doi.org/10.4172/2167-0846.1000216.
34. Geller M, Mibielli MA, Nunes CP et al. Comparison of the action of diclofenac alone versus diclofenac plus B vitamins on mobility in patients with low back pain. J Drug Assess. 2016; 5(1): 1-3. http://doi.org/10.3109/21556660.2016.1163263.
35. Cooper C, Chapurlat R, Al-Daghri N et al. Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Drugs Aging. 2019; 36: 15-24.
36. Elliott WJ. Do the blood pressure effects of nonsteroidal antiinflammatory drugs influence cardiovascular morbidity and mortality? Curr Hypertens Rep. 2010; 12: 258-66.
37. Chan CC, Reid CM, Aw T-J et al. Do COX-2 inhibitors raise blood pressure more than nonselective NSAIDs and placebo? An updated meta-analysis. J Hypertens. 2009; 27(12): 2332-41. http://doi.org/10.1097/hjh.0b013e3283310dc9.
38. Brater DC. Resistance to Loop Diuretics Why it Happens and What to Do About It. Drugs. 1985; 30(5): 427-43. http://doi.org/10.2165/00003495-198530050-00003.
39. Laiwah AC, Mactier RA. Antagonistic effect of non-steroidal anti-inflammatory drugs on frusemide-induced diuresis in cardiac failure. Br Med J. 1981; 283(6293): 714.
40. Bhagat K. Effects of non-steroidal anti-inflammatory drugs on hypertension control using angiotensin converting enzyme inhibitors and thiazide diuretics. East Afr Med J. 2001; 78: 507-9.
41. Palmer R, Weiss R, Zusman RM et al. Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors. Am J Hypertens. 2003; 16: 135-9.
42. White WB. Defining the problem of treating the patient with hypertension and arthritis pain. Am J Med. 2009; 122: S3-9.
43. Webster J. Interactions of NSAIDs with diuretics and beta-blockers mechanisms and clinical implications. Drugs. 1985; 30: 32-41.
44. Krum H, Swergold G, Curtis SP et al. Factors associated with blood pressure changes in patients receiving diclofenac or etoricoxib: results from the MEDAL study. J Hypertens. 2009; 27: 886-93.
45. Pavlicević I, Kuzmanić M, Rumboldt M et al. Interaction between antihypertensives and NSAIDs in primary care: a controlled trial. Can J Clin Pharmacol. 2008; 15: e372-82.
46. Sharman JE, La Gerche A, Coombes JS. Exercise and cardiovascular risk in patients with hypertension. Am J Hypertens. 2015; 28: 147-58.
47. Dong Y-H, Chang C-H, Wu L-C et al. Comparative cardiovascular safety of nonsteroidal anti-inflammatory drugs in patients with hypertension: a population-based cohort study. Br J Clin Pharmacol. 2018; 84: 1045-56.
48. Bruno A, Tacconelli S, Patrignani P. Variability in the response to non-steroidal anti-inflammatory drugs: mechanisms and perspectives. Basic Clin Pharmacol Toxicol. 2014; 114: 56-63.
49. Odom DM, Mladsi DM, Saag KG et al. Relationship between diclofenac dose and risk of gastrointestinal and cardiovascular events: meta-regression based on two systematic literature reviews. Clin Ther. 2014; 36: 906-17.
50. Moore N, Salvo F, Duong M et al. Cardiovascular risks associated with low-dose ibuprofen and diclofenac as used OTC. Expert Opin Drug Saf. 2014; 13: 167-79.
51. García Rodríguez LA, Tacconelli S, Patrignani P. Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population. J Am Coll Cardiol. 2008; 52(20): 1628-36.
52. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011; 8: e1001098.
53.Varas-Lorenzo C, Castellsague J, Stang MR et al. The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada. Pharmacoepidemiol Drug Saf. 2009; 18(11): 1016-25. http://doi.org/10.1002/pds.1815.
54. Andersohn F, Suissa S, Garbe E. Use of First- and Second-Generation Cyclooxygenase-2–Selective Nonsteroidal Antiinflammatory Drugs and Risk of Acute Myocardial Infarction. Circulation. 2006; 113(16): 1950-7. http://doi.org/10.1161/CIRCULATIONAHA.105.602425.
55. Salvo F, Antoniazzi S, Duong M et al. Cardiovascular events associated with the long-term use of NSAIDs: a review of randomized controlled trials and observational studies. Expert Opin Drug Saf. 2014; 13: 573-85.
56. Abdulmajeed NA, Alnahdi HS, Ayas NO et al. Amelioration of cardiotoxic impacts of diclofenac sodium by vitamin B complex. Eur Rev Med Pharmacol Sci. 2015; 19: 671-81.
57. Tanaka T, Kono T, Terasaki F et al. Thiamine prevents obesity and obesity-associated metabolic disorders in OLETF rats. J Nutr Sci Vitaminol. 2010; 56: 335-46.
58. Babaei-Jadidi R, Karachalias N, Kupich C et al. High-dose thiamine therapy counters dyslipidaemia in streptozotocin-induced diabetic rats. Diabetologia. 2004; 47(12): 2235-46.
59. Earnest CP, Wood KA, Church TS. Complex multivitamin supplementation improves homocysteine and resistance to LDL-C oxidation. J Am Coll Nutr. 2003; 22: 400-7.
60. Göksemin A, Sati L, Seval Y et al. Effects of Excess Vitamin B6 Intake on Serum Lipid Profile and Cerebral Cortex in Rats. Turk J Med Sci. 2006; 36(6): 327-35.
61. Schuijt MP, Huntjens-Fleuren HWHA, de Metz M et al. The interaction of ibuprofen and diclofenac with aspirin in healthy volunteers. Br J Pharmacol. 2009; 157: 931-4.
62. Catella-Lawson F, Reilly MP, Kapoor SC et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001; 345: 1809-17.
63. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. 2019.
64. Diclofenac-containing medicines 2013.
65. Altman R, Bosch B, Brune K et al. Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology. Drugs. 2015; 75: 859-77.